There is a constantly growing need to produce proteins like enzymes, antibodies or hormones for use in therapeutic applications. Currently used state of the art heterologous protein production systems include prokaryotic and eukaryotic cell systems like E. coli, yeast, viruses, fungi and insect cells. In order to produce recombinant proteins which require post- or peri-translational modifications such as glycosylation (and where industrial scale production is needed) very often mammalian cell systems including cells from Cricetulus griseus, Cercopithecus aethiops, Homo sapiens, Mesocricetus auratus, Mus musculus and Chlorocebus species are used. Mammalian cell systems have become a routine production system for therapeutic proteins and antibodies. Said cells have been characterized extensively in the recent history, they can reach extremely high production levels, can be free of infectious or virus like particles, can grow to very high density in bioreactors and they can be genetically manipulated and transformed. For example, Chinese Hamster Ovary (CHO) cells can be engineered to resemble the human glycan profile by transfection of the appropriate glycosyl transferases. Recombinantly produced growth factors are already widely used in therapeutic applications or are promising candidates for the development of new therapies. However, expression of growth hormones in mammalian cells, for example CHO cell lines can result in cell growth inhibition and low titers.
In the near future more and more “non-antibody” protein formats will be part of the pipelines of pharmaceutical companies. However, expression of extracellular signaling molecules as growth factors, hormones, neurotransmitters and cytokines at large scale may not be possible in mammalian cell lines due to growth inhibition resulting in low titers. It is thus clearly desirable to have access to suitable methods for producing growth factors and other therapeutic proteins at industry scale.